ADVERTORIAL: Answering the question of durability is TAVI’s next challenge

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Vinayak Bapat

Over the past few years, the indications for transcatheter aortic valve implantation (TAVI) have expanded from inoperable patients to low-risk patients—meaning that TAVI can now be considered for all aortic stenosis patients, regardless of their surgical risk.1 However, using TAVI in lower risk patients does raise the question of the durability of TAVI valves. This article explores what we know about the durability of TAVI valves and why pipeline TAVI technologies may address the challenges of durability.

Dr Vinayak Bapat (Division of Cardiac Surgery, Columbia University Medical Center, New York, USA) explains that the expanding indications of TAVI mean that younger and lower risk patients who were previously considered for surgical aortic valve replacement are now being considered for TAVI. Guideline recommendations for a tissue valve are based on durability data of surgical valves and, hence, to recommend TAVI in these patients means that durability becomes important. He says: “Haemodynamics and durability are the next most important thing for TAVI as the long- term durability of TAVI valves is still unclear. Therefore, the next challenge for TAVI devices is to address this issue.”

For Dr Bapat, with most patients over the age of 70 years, the goal of a valve replacement is for the valve to last the lifetime of the patient. He comments “Implant once and then you are done with it; that is a very appealing idea.” Though for younger patients (i.e. under 70 years old), the aim would be more to get them to over 70 years old before having to reintervene. Ultimately, according to Dr Bapat—keeping in mind that tissue valves do not last as long in younger patients—expecting a TAVI valve to last eight to 10 years is reasonable. “If we can get 10 years out of a TAVI valve in younger patients, I think most of us who use TAVI will be quite happy.”

Lack of data

At present, whether a TAVI valve will last 10 years before deteriorating is unknown. Earlier this year, Dr Daniel Blackman (Department of Cardiology, Leeds Teaching Hospital NHS Trust, Leeds, UK) and colleagues published data in the Journal of the American College of Cardiology for the long-term durability of TAVI prostheses.2 They reviewed 241 patients who underwent TAVI between 2007 and 2011, reporting that their study represents “the largest cohort of patients with echocardiographic assessment of valve function between five and 10 years”.

The authors found that “overall, long-term function of transcatheter heart valves were excellent, with no increase in average peak gradient, and a reduction in aortic regurgitation at long-term follow-up”. Furthermore, they note that structural valve deterioration was “very rare” with only one case of severe deterioration and 21 cases of moderate deterioration.

However, Blackman et al report that a limitation of their study was that the medium long-term follow-up was only 5.8 years “with fewer than 15% having follow-up beyond eight years”. In fact, in the study:

  • 69% had six-year follow-up
  • 28% had seven-year follow-up
  • 12% had eight-year follow-up
  • 4% had nine-year follow-up
  • Only 1% had 10-year data.

“Longer-term data is needed for more robust analysis; we plan to continue follow-up of the study cohort and report annually on valve durability,” they observe. Additionally, they state: “The findings of this study cannot be extrapolated to younger patients, in whom TAVI may be considered in preference to surgical valve replacement in the future, and in whom valve durability will be the pivotal consideration.”

Durability of future generation TAVI devices is critical

Dr Bapat says that a key consideration for ensuring long-term durability of pipeline TAVI technologies is choosing the right material for the prosthesis as well as having the correct valve structure. Today bovine pericardium and porcine pericardium are used in the current generation of TAVI devices. “The aim is to minimise calcification; durability is all about how slowly the valve calcifies,” he comments. Each manufacturer has proprietary method of decalcifying pericardium.

According to Dr Bapat, a material that is developed and manufactured by Admedus, currently being used for surgically repairing congenital heart defects, may have potential as a durable material for a TAVI device. He states that, during the manufacturing process, all nucleic acid are removed—making it “an acellular pure collagen scaffold”. Furthermore, Neethling et al3 report that steps are taken to eliminate cytotoxicity by the ADAPT Tissue Engineering process.” Dr Bapat comments that, with the ability to have “absolutely no toxicity or immunogenicity”, use of ADAPT material in a TAVI device would be a step forward in terms of durability compared to many current TAVI valves on the market”.

Admedus are now developing the use of the ADAPT technology in TAVI valves on back of the 10-year data that are available for the ADAPT-treated BioScaffold in younger patients. These data demonstrated zero calcification over that period. Dr William Neethling (School of Surgery, University of Western Australia, Perth, Australia) and colleagues performed a retrospective analysis of 30 patients with congenital heart defects who had been implanted with the scaffold between April 2008 and September 2009.5 The median age of the patients was 18 months and 10-year follow-up was available for 25 patients. At 10 years, they found no graft-related mortality, graft failure, thromboembolic events, or infections. Also, no device-related reinterventions were required. The authors conclude: “ADAPT treated BioScaffold demonstrated excellent medium to long-term (up to 10 years) performance when used as a bioscaffold for repair of congenital heart defects in children. [The] durability, acellularity, biostability, and non-calcifying potential of ADAPT treated BioScaffolds makes it a very attractive tissue substitute for congenital cardiac repair procedures.”

A study published The Annals of Thoracic Surgery this year (2019) provide further durability data for the scaffold.6 Authors Dr Douglas Bell (UQ School of Medicine, University of Queensland, Brisbane, Australia) and others report that after a median follow-up of 31 months (range 1 to 60 months), no echocardiographic or radiological evidence of patch calcification was observed for 501 implants (in 377 patients) of the scaffold. They add that, overall, the rate of freedom from intervention between three and five years was 96%. “ADAPT Treated BioScaffold has good durability when used for the repair of congenital heart defects. It performs comparably in the systematic and pulmonary circulations in neonates, infants, and older children,” the authors conclude.

As for the Admedus TAVI system, the company plans to initiate first-in-human studies for its single-piece 3D aortic valve next year (2020).4 Based on Admedus’ current laboratory and animal study findings combined with the highly differentiated anticalcification properties of all products generated using the ADAPT technology, according to Admedus, there is a real potential for single- piece 3D aortic valve TAVI devices to be a breakthrough for patients.

This advertorial was sponsored by Admedus. The views expressed are those of the company and the quoted physicians. They do not necessarily represent those of BIBA Medical/Cardiovascular News.

 

 

References

  1. Edwards Lifesciences. Edwards Sapien 3 TAVI receives expanded approval in Europe. Cision PR Newswire. https://prn.to/2qMk6F4 (date accessed 13 November 2019).
  2. Blackman DJ, Saraf S, MacCarthy PA, et al. Long-term durability of transcatheter aortic valve prostheses. J Am Coll Cardiol 2019; 73(5): 537–45.
  3. Neethling WM, Strange G, Firth L, et al. Evaluation of a tissue-engineered bovine pericardial patch in paediatric patients with congenital cardiac anomalies: initial experience with the ADAPT-treated CardioCel(R) patch. Interact Cardiovasc Thorac Surg 2013; 17(4): 698–702.
  4. Admedus limited. Admedus inks $A36.2M deal for CardioCel and VascuCel patch business. Cision PR Newswire. https://prn.to/34RZ6LM (date accessed 13 November 2019).
  5. Neethling WM, Forster G, and Bhirangi K. Performance of the ADAPT-treated CardioCel bioscaffold in paediatric patients with congenital cardiac anomalies: Medium to long-term outcomes. Presented at the 2019 ESCHSA-WSPCHS Joint Meeting (20–22 June, Sofia, Bulgaria).
  6. Bell D, Betts K, Justo R, et al. Multicenter experience with 500 CardioCel implants used for the repair of congenital heart defects. Ann Thorac Surg 2019. Epub.

 

 


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